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At least 307 records · Page 17Linked to original sources

PubMed2005

Evidence for ineffective erythropoiesis in severe sickle cell disease.

Peripheral destruction of sickled erythrocytes is a cardinal feature of sickle cell disease (SCD). Less well established is the potential contribution of ineffective erythropoiesis to the pathophysiology of this hemoglobinopathy. Since patients with SCD frequently develop mixed hematopoietic chimerism after allogeneic nonmyeloablative stem cell transplantation, we used this opportunity to directly compare the differentiation and survival of SCD and donor-derived erythropoiesis in vivo. Donor and recipient erythropoiesis was compared in 4 patients with SCD and 4 without SCD who developed stable mixed hematopoietic chimerism following transplant. Molecular analysis of chimerism in peripheral blood and bone marrow demonstrated higher expression of donor-derived beta-globin RNA relative to the level of donor-derived genomic DNA in patients with SCD. Analysis of chimerism in immature (glycophorin A-positive [GYPA(+)], CD71(hi)) and mature (GYPA(+), CD71(neg)) erythroblasts confirmed the intramedullary loss of SS erythroblasts with progressive maturation. In patients with SCD, relative enrichment of donor erythroid precursors began to appear at the onset of hemoglobinization. Ineffective erythropoiesis of homozygous hemoglobin S (SS) progenitors thus provides a maturation advantage for homozygous hemoglobin A (AA) or heterozygous hemoglobin S/hemoglobin A (SA) donor erythroid precursor cells that results in greater donor contribution to overall erythropoiesis following stem-cell transplantation and improvement of clinical disease.

Adult↗

PubMed1995

Combined immunocytochemistry and non-isotopic in situ hybridization for the ultrastructural investigation of human parvovirus B19 infection.

Parvovirus B19 is a single-stranded DNA virus with a specific tropism for human erythroid precursor cells. The virus codes for two overlapping structural (capsid) proteins and one non-structural protein which is thought to perform essential functions in viral replication, transcription and packaging. The ultrastructural localization of these proteins was achieved in cultured haemopoietic cells derived from fetal liver which had been infected in vitro and subsequently embedded in LR White acrylic resin. Postembedding immunogold detection of B19 structural and non-structural proteins was combined with localization of viral nucleic acid by in situ hybridization using a digoxigenin-labelled probe and different sized gold labels. The majority of the B19 capsid protein and DNA present in cells harvested 48 hours post-infection co-localized within the centri-nuclear region of erythroid cells demonstrating characteristic chromatin margination. Relatively little DNA hybridization signal was present over paracrystalline inclusions strongly labelled with anti-capsid protein monoclonal antibody R92F6. Viral DNA and capsid protein were co-localized in apparent egress from the nucleus through nuclear pores. B19 non-structural protein was detected in association with both nuclear and cytoplasmic arrays of capsids, supporting the view that this protein plays an important role in viral packaging and remains associated with the complete viral particle until its release from the cell. Co-localization of viral nucleic acid and proteins at the ultrastructural level is a flexible, rapid and highly specific tool for examination of viral life-cycles within cells.

Capsid↗

PubMed1985

Protective effect of testosterone or 5 beta-dihydrotestosterone pretreatment on CFU-E numbers in busulfan-treated rabbits.

Busulfan is known to damage hematological stem cells. On the other hand, numerous steroid hormones have a stimulating effect on hematopoiesis. We wished to find out whether steroids have a protective effect on hematopoiesis in the case of busulfan treatment. This possibility was tested in vitro in rabbit bone marrow cultures, with and without in vivo pretreatment, with regard to erythropoiesis. The stimulating effect of testosterone or 5 beta-dihydrotestosterone on the CFU-E number in rabbit bone marrow cultures was blocked in the presence of busulfan. When rabbits were pretreated with either steroid before the administration of busulfan, however, the reduction of the CFU-E number seen after busulfan therapy alone was compensated. These results indicate that testosterone and the nonandrogenic 5 beta-dihydrotestosterone provide some protective effect on erythroid precursor cells when administered with reference to the cell-cycle-dependent action of busulfan.

Animals↗

PubMed1989

Increased erythrocyte adenosine deaminase activity in children with perinatal human immunodeficiency virus infection.

Erythrocyte adenosine deaminase (ADA) activity was assessed in 33 children born to human immuno-deficiency virus (HIV)-positive mothers. The enzyme values were significantly increased in infected, symptom-free children compared with a control group of HIV-negative subjects (mean +/- SD: 0.34 +/- 0.01 unit/ml red blood cells (RBC) vs. 0.25 +/- 0.04 unit/ml RBC, P less than 0.01) and a further significant increase was found in symptomatic children (0.45 +/- 0.02 unit/ml RBC, P less than 0.01 vs. infected, symptom-free children). ADA values were slightly enhanced also in the group of infants in whom the state of HIV infection was indeterminate (0.29 +/- 0.03 unit/ml RBC, P not significant vs. controls). These data indicate that increased erythrocyte ADA activity may be a useful though indirect marker of HIV infection in children at risk and be of possible prognostic relevance. Since increased values were present also in children without overt infections or hematologic disorders, and ADA activity of erythrocytes obtained from healthy donors did not increase after 1 hour incubation with patients' serum, HIV could induce large amounts of cellular enzyme infecting directly erythroid precursor cells.

Adenosine Deaminase↗

PubMed2001

Cessation of intensive treatment with recombinant human erythropoietin is followed by secondary anemia.

Little information is available on the evolution of erythropoiesis after interruption of recombinant human erythropoietin (rHuEpo) therapy. Iron-overloaded rats received 20 daily injections of rHuEpo. During treatment, reticulocytes, soluble transferrin receptor (sTfR), and hematocrit increased progressively. This was accompanied by a substantial expansion of spleen erythropoiesis but a decrease in the bone marrow. Five weeks after treatment, rats developed a significant degree of a regenerative anemia. Erythropoietic activity, as assessed by reticulocytes, sTfR, erythroid cellularity, iron incorporation into heme, and the number of erythroid colonies, was severely depressed 3 weeks after cessation of rHuEpo. This was followed by regeneration of erythroblasts and reticulocytes at weeks 6 to 7 post-Epo, but erythroid progenitors recovered only partially by that time. The anemia was definitely corrected 2 months after cessation of rHuEpo treatment. Serum Epo levels remained elevated for several weeks, but the sensitivity of marrow erythroid precursors to Epo was preserved. No rat antibodies to rHuEpo were detected, and serum from post-Epo animals did not exert any inhibitory activity on erythropoiesis. In conclusion, after cessation of intensive rHuEpo therapy, there was a strong inhibition of erythropoietic activity with secondary anemia followed by late recovery. This was not due to antibodies or other soluble inhibitory factors, a defect in endogenous Epo production, or a loss of sensitivity to Epo. This may rather represent intrinsic erythroid marrow exhaustion, mostly at the level of erythroid progenitors but also at later stages of erythropoiesis.

Anemia↗

PubMed1992

Characterization of primitive hematopoietic cells in normal human peripheral blood.

The total number of clonogenic cells present in 5-week-old long-term cultures (LTC) initiated by seeding normal human marrow cells on competent adherent cell feeder layers allows for the quantitation of a more primitive hematopoietic input precursor cell type referred to as an LTC-initiating cell (LTC-IC). Previous studies have suggested that LTC-IC also circulate because production of clonogenic cells continues for many weeks when cells from the light-density (< 1.077 g/mL), T-cell-depleted fraction of normal blood are maintained on irradiated, marrow-derived feeder layers in LTC medium. We now show that the number of clonogenic cells present in such reconstructed LTC after 5 weeks is linearly related to the input number of peripheral blood (PB) cells over a wide range of cell concentrations, thereby permitting the quantitation of circulating LTC-IC by limiting dilution analysis. Using this approach, we have found the concentration of LTC-IC in the circulation of normal adults to be 2.9 +/- 0.5/mL. This is approximately 75-fold lower than the concentration of circulating clonogenic cells (ie, burst-forming units-erythroid plus colony-forming units [CFU] granulocyte-macrophage plus CFU-granulocyte, erythroid, monocyte, megakaryocyte) and represents a frequency of LTC-IC relative to all nucleated cells that is approximately 100-fold lower than that measured in normal marrow aspirate samples. Characterization studies showed most circulating LTC-IC to be small (low forward light scatter and side scatter), CD34+, Rh-123dull, HLA-DR-, and 4-hydroperoxycyclophosphamide-resistant cells, with differentiative and proliferative potentialities indistinguishable from LTC-IC in normal marrow. Isolation of the light-density, T-cell-depleted, CD34+, and either HLA-DR(low) or Rh-123(dull) fraction of normal blood yielded a highly enriched population of cells that were 0.5% to 1% LTC-IC (approximately 1,500-fold enriched beyond the light-density, T-cell-depletion step), a purity comparable to the most enriched populations of human marrow LTC-IC reported to date. However, purification of PB LTC-IC on the basis of these properties did not allow them to be physically separated from a substantial proportion (> 30%) of the clonogenic cells in the same samples, in contrast to previous findings for LTC-IC and clonogenic cells in marrow. These studies show the presence in the blood of normal adults of a relatively small but readily detectable population of functionally defined, primitive hematopoietic cells that share properties with marrow LTC-IC, a cell type thought to have in vivo reconstituting potential.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1995

Improvement of anemia in W/WV mice by recombinant human erythropoietin (rHuEPO) mediated through EPO receptors with lowered affinity.

We studied the effects of recombinant human erythropoietin (rHuEPO) on anemic W/WV mice which manifested severe anemia accompanied by mutation of the W gene encoding tyrosine kinase type receptor (c-kit gene) of bone marrow hematopoietic cells. Nine-week-old male W/WV mice or normal littermates (+/+) were used. Since serum EPO concentration in W/WV mice increased in proportion to severity of anemia, EPO production in the kidneys of these animals was found to be regulated normally. Hematocrit in +/+ mice increased and a maximal response was also obtained with 2,000 IU/kg of rHuEPO. On the other hand, hematocrit in W/WV mice increased in a dose-responsive manner by administration with 2,000 and 10,000 IU/kg, showing different responses to rHuEPO in these two types of mice. The responsiveness of W/WV mice to rHuEPO was low in terms of increases in erythroblastic precursor cells (CFU-E), and immature cells in the bone marrow. Scatchard analysis of the specific binding of 125I-rHuEPO against bone marrow cells revealed that the different responsiveness to rHuEPO between W/WV and +/+ mice may be correlated with differences in affinity of EPO receptor of bone marrow cells in these mice. From these results, a high dose of rHuEPO is capable of improving the anemia in W/WV mice that had EPO receptors with lowered affinity, indicating the possible effectiveness of rHuEPO in anemic patients with EPO receptor abnormality.

Anemia↗

PubMed1998

Delayed onset of hemolytic anemia in CBA-Pk-1slc/Pk-1slc mice with a point mutation of the gene encoding red blood cell type pyruvate kinase.

The Pk-1slc gene encodes a mutant red blood cell (RBC) type pyruvate kinase (PK), and adult CBA-Pk-1slc/Pk-1slc mice show a severe nonspherocytic hemolytic anemia. However, the number of RBCs and the proportion of reticulocytes were comparable between neonatal CBA-Pk-1slc/Pk-1slc mice and control -+/+ mice. Since the age-dependent increase of RBCs was much greater in CBA-+/+ mice than in CBA-Pk-1slc/Pk-1slc mice, significant anemia was observed in the latter mice on day 14 after birth. The increase of RBCs in CBA-+/+ mice was due to the prolongation of their survival time. The half life of RBCs increased in CBA-+/+ mice with ages, but it decreased in CBA-Pk-1slc/Pk-1slc mice. The relatively longer half life of RBCs in neonatal CBA-Pk-1slc/Pk-1slc mice appeared to be due to the delayed switching from M2-type PK that are expressed by undifferentiated erythroid precursor cells to RBC-type PK that are expressed by mature RBCs.

Age of Onset↗

PubMed2003

Origin, precursors and differentiation of mouse dendritic cells.

Functional specialization allows defined dendritic-cell (DC) subsets to induce efficient defence mechanisms against pathogens and tumour cells, and maintain T-cell tolerance by inducing the inactivation of autoreactive T cells. A crucial question, which has important implications for both our understanding of the induction and control of immunity by DCs, as well as the use of DCs for immunotherapy, is whether the functional diversity of DCs results from the existence of developmentally independent DC subpopulations, or whether DC subsets that share a common differentiation origin acquire specific functions in response to environmental signals. This review discusses recent findings on mouse DC development.

Animals↗

PubMed2003

Capecitabine treatment results in increased mean corpuscular volume of red blood cells in patients with advanced solid malignancies.

Capecitabine is a novel fluoropyrimidine carbamate which is selectively activated after oral administration to 5-fluorouracil (5-FU) by a sequential triple enzyme pathway in liver and tumor cells. The cytotoxic activity of the metabolized 5-FU depends on thymidylate synthase (TS) inhibition, leading to defective DNA synthesis. Capecitabine has shown promising activity in all tumor types sensitive to 5-FU and is therefore investigated in many clinical trials. Since we observed an increase of mean corpuscular volume (MCV) of red blood cells under therapy with capecitabine, the current investigation aimed to quantitate this effect and to elucidate the underlying mechanisms. A total of 154 patients suffering from advanced cancer received capecitabine (2500 mg/m2/day for 14 days every 21 days) either as monotherapy, or in combination with other antineoplastic agents or biological response modifiers. During 3 consecutive cycles of therapy a complete blood cell count including the red cell indices MCV, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration was performed before each application of capecitabine. In addition, vitamin B12, folic acid and homocysteine were determined to define their role in increasing MCV. Restaging was performed after 9 weeks. Within 9 weeks, a statistically significant increase of MCV (without other hematologic abnormalities or clinical symptoms) could be observed (p<0.0001). Vitamin B12, folic acid and homocysteine levels did not change significantly during the observation period. When comparing the different increases of MCV during 9 weeks (deltaMCV) with respect to tumor response, deltaMCV tended to higher values in patients with tumor remission or stable disease than in patients with tumor progression. We conclude that serum levels within the normal range rule out severe deficiencies of vitamin B12, folic acid or homocysteine as an account of macrocytemia. We therefore hypothesize that an increased MCV (without concomitant anemia) in patients receiving capecitabine might be due to the 5-FU-induced TS inhibition also in erythroid precursor cells. Whether this increase in MCV might serve as a surrogate marker for tumor response has to be evaluated in further investigations.

Antimetabolites, Antineoplastic↗

PubMed2001

The fetal liver counterpart of adult common lymphoid progenitors gives rise to all lymphoid lineages, CD45+CD4+CD3- cells, as well as macrophages.

We identified an IL-7Ralpha(+)Sca-1(low)c-Kit(low) population in E14 fetal liver, which is the phenotypical analog of common lymphoid progenitors (CLP) in adult bone marrow. After transfer into newborn mice, the IL-7Ralpha(+)Sca-1(low)c-Kit(low) population rapidly differentiated into CD45(+)CD4(+)CD3(-) cells, which are candidate cells for initiating lymph node and Peyer's patch formation. In addition, this population also gave rise to B, T, NK, and CD8alpha(+) and CD8alpha(-) dendritic cells. The fetal liver precursors expressed a significantly lower level of the myeloid-suppressing transcription factor Pax-5, than adult CLP, and retained differentiation activity for macrophages in vitro. We propose that the transition from fetal liver IL-7Ralpha(+)Sca-1(low)c-Kit(low) cells to adult CLP involves a regulated restriction of their developmental potential, controlled, at least in part, by Pax-5 expression.

Animals↗

PubMed1996

Complexity of the erythroid transcription factor NF-E2 as revealed by gene targeting of the mouse p18 NF-E2 locus.

High-level globin expression in erythroid precursor cells depends on the integrity of NF-E2 recognition sites, transcription factor AP-1-like protein-binding motifs, located in the upstream regulatory regions of the alpha- and beta-globin loci. The NF-E2 transcription factor, which recognizes these sites, is a heterodimer consisting of (i) p45 NF-E2 (the larger subunit), a hematopoietic-restricted basic leucine zipper protein, and (ii) a widely expressed basic leucine zipper factor, p18 NF-E2, the smaller subunit. p18 NF-E2 protein shares extensive homology with the maf protooncogene family. To determine an in vivo role for p18 NF-E2 protein we disrupted the p18 NF-E2-encoding gene by homologous recombination in murine embryonic stem cells and generated p18 NF-E2-/- mice. These mice are indistinguishable from littermates throughout all phases of development and remain healthy in adulthood. Despite the absence of expressed p18 NF-E2, DNA-binding activity with the properties of the NF-E2 heterodimer is present in fetal liver erythroid cells of p18 NF-E2-/- mice. We speculate that another member of the maf basic leucine zipper family substitutes for the p18 subunit in a complex with p45 NF-E2. Thus, p18 NF-E2 per se appears to be dispensable in vivo.

Animals↗

PubMed2001

Paclitaxel pharmacodynamics: application of a mechanism-based neutropenia model.

Antineoplastic agents exert adverse effects that impact both dose and scheduling of drug administration. Our objective was to develop a quantitative relationship between paclitaxel (taxol) exposure and pharmacodynamic endpoints, such as neutropenia or body weight loss. Paclitaxel in liposomes or Cremophor EL was administered to rats at doses of 20 or 40 mg/kg. Body weight and absolute neutrophil count were determined daily. The decrease in body weight was greater for paclitaxel in Cremophor EL than for liposomal paclitaxel, but hematological toxicity was similar. The hematological data was fit using a pharmacodynamic model to investigate the temporal delay between drug exposure and neutropenia. From the model, the lifespan of neutrophils (T(N)), of surviving precursor cells in bone marrow (T(P)), and a killing rate constant (K) were determined. The values of T(N), T(P), and K for liposomal paclitaxel were 95 h, 82 h, and 0.735 (microM h)(-1), respectively, and for paclitaxel in Cremophor EL, 86 h, 78 h, and 0.475 (microM h)(-1), respectively. Simulations of various doses indicated a dependency of the neutropenia time course on paclitaxel exposure. The entire time course of changes in neutrophil count is more informative than a single measurement if myelosuppression is prolonged and at a level associated with increased incidence of clinical adverse effects.

Animals↗

PubMed1997

The role of cytoskeletal elements in the two-phase denucleation process of mammalian erythroblasts in vitro observed by laser confocal scanning microscope.

The cytoskeletal elements in the denucleation processes were observed using immunofluorescence and laser confocal scanning microscopy in the Friend virus (FVA) infected splenic erythroblasts of BALB/c mice. When cultured in the presence of erythropoietin (EPO), it was shown that the synchronized erythroid precursor cells proceeded to an autonomous nuclear extrusion when the three types of cytoskeletal elements were observed contributing to different phases of that process. The vimentin intermediate filament (IF) was shown as the nuclear anchorage elements with binding sites anchored from the nuclear lamina to the center as well as to the plasma membrane periphery. A dense perinuclear layer of vimentin fluorescence in erythroblasts was observable during the periods of 12, 24 and 36 hrs. in vitro culture. The amount of vimentin IF per cell was higher than that of tubulin and F-actin at 12-24 hrs. culture, but the vimentin filaments were observed to brake down and decreased steadily when the cells became differentiated into late erythroblasts at 36-48 hrs. Such an attenuation of vimentin filaments may facilitate the eccentric movement of the nucleus which can be regarded as the initial step (phase) of denucleation. The fluorescent intensity of tubulin and actin exhibited a significant rise and aggregated between the extruding nucleus and the incipient reticulocyte prior to and during the processes of denucleation, what indicated that the actin filaments and microtubules may play roles in the second phase of the denucleation process, or final commitment of enucleation. The erythroid differentiation-denucleation factor (EDDF), as an intrinsic factor, involved in the denucleation events, was also discussed.

Animals↗

PubMed2001

Dendritic cell potentials of early lymphoid and myeloid progenitors.

It has been proposed that there are at least 2 classes of dendritic cells (DCs), CD8alpha(+) DCs derived from the lymphoid lineage and CD8alpha(-) DCs derived from the myeloid lineage. Here, the abilities of lymphoid- and myeloid-restricted progenitors to generate DCs are compared, and their overall contributions to the DC compartment are evaluated. It has previously been shown that primitive myeloid-committed progenitors (common myeloid progenitors [CMPs]) are efficient precursors of both CD8alpha(+) and CD8alpha(-) DCs in vivo. Here it is shown that the earliest lymphoid-committed progenitors (common lymphoid progenitors [CLPs]) and CMPs and their progeny granulocyte-macrophage progenitors (GMPs) can give rise to functional DCs in vitro and in vivo. CLPs are more efficient in generating DCs than their T-lineage descendants, the early thymocyte progenitors and pro-T cells, and CMPs are more efficient DC precursors than the descendant GMPs, whereas pro-B cells and megakaryocyte-erythrocyte progenitors are incapable of generating DCs. Thus, DC developmental potential is preserved during T- but not B-lymphoid differentiation from CLP and during granulocyte-macrophage but not megakaryocyte-erythrocyte development from CMP. In vivo reconstitution experiments show that CLPs and CMPs can reconstitute CD8alpha(+) and CD8alpha(-) DCs with similar efficiency on a per cell basis. However, CMPs are 10-fold more numerous than CLPs, suggesting that at steady state, CLPs provide only a minority of splenic DCs and approximately half the DCs in thymus, whereas most DCs, including CD8alpha(+) and CD8alpha(-) subtypes, are of myeloid origin. (Blood. 2001;97:3333-3341)

Animals↗

PubMed2000

Disruption of the homeobox gene Hoxb-6 in mice results in increased numbers of early erythrocyte progenitors.

Hox genes encode transcription factors that are required for proper development of certain tissues and for patterning of the hindbrain, the limbs, and skeleton. They are also expressed in the hematopoietic system with a preference for specific cell lineages. To determine the role of Hoxb-6 in normal hematopoiesis, mice with a targeted disruption in the Hoxb-6 gene were generated. Mature hematopoietic cell types and immune responses are normal in homozygous Hoxb-6 mutants. Clonogenic progenitor cell assays demonstrate an increased number of early erythroid progenitor cells in the bone marrow and fetal liver of mutants, while differentiation of other cell lineages is unaffected. These results suggest that Hoxb-6 controls the generation, proliferation, or survival of erythroid progenitor cells.

Animals↗

PubMed1997

Effects of multiple doses of T-2 toxin on the erythroid response capacity of mice following an extensive experimental bleeding.

Total nucleated cellularity and total erythroid cell populations were measured in spleen and bone marrow of mice at different times after treatment with 3 daily doses of T-2 toxin (2.0 mg/kg). It was found that the initial depletion of hematopoietic cells produced by the toxin was rapidly reverted in spleen, giving way after 48 hr to a significant hypercellularity which after 10 days was 2.5 times the normal levels, but this effect was not observed in bone marrow, which slowly recovered normal cellularity after 5 days. The cytological analysis revealed that there was a highly significant shift in the ratio of erythroid to non-erythroid cells, since erythroid cell populations increased by about 8-fold in spleen and nearly 2-fold in bone marrow between 10 and 35 days after intoxication. In order to test the integrity of the hematopoietic reserve capacity, a hemorrhagic stress was produced in intoxicated animals at 10-50 days after toxin exposure. It was found that the erythroid response capacity was significantly higher in the intoxicated animals compared to anemic controls. The results suggest that the initial cytotoxic damage produced by T-2 toxin in the hematopoietic system is followed by a significant erythroid hypercellularity, which can confer an increased capacity for response to a hemorrhagic emergency.

Animals↗

PubMed1994

Fetal hemoglobin synthesis in sickle cell anemia: some molecular considerations.

An ability to maintain high levels of fetal hemoglobin (Hb F) has been associated with the amelioration of the clinical severity of the sickle cell disease (SS). Clinical efforts to increase the Hb F level of the patients have, however, yielded variable therapeutic response. In an attempt to further elucidate the underlying molecular basis, in vitro Hb F synthesis was studied in erythroid progenitor (BFU-E) cells obtained from SS patients and their heterozygous (AS) relatives with varying genetic backgrounds. This allows us to study the Hb F biosynthesis pattern uncomplicated by the influence of the preferential survival of "F cells" in vivo. The Hb F levels and the relative concentrations of its constituent gamma globin chains, G gamma and A gamma, were assayed using the reversed phase HPLC method. A percentage increase in the fetal hemoglobin content was observed in the lysates of the erythroid progenitor cells relative to the circulating peripheral blood erythrocyte values in SS patients and their AS relatives with different beta S haplotypes reflecting the intrinsic capacity of fetal hemoglobin synthesis in these subjects. No such increase was observed in the patient with the Mor haplotype. Furthermore, the Hb F synthesized in the BFU-E colonies was more of the adult type, as evidenced by the decrease in the percent G gamma level relative to the corresponding peripheral blood values of the subjects in all the haplotype groups studied. The Mor haplotype was again an exception, synthesizing fetal hemoglobin more of the fetal type.

Anemia, Sickle Cell↗